The 29-year-old centre-back was substituted during Sunday’s derby defeat by Liverpool with a hamstring injury and has not recovered in time.
Manager David Moyes has Jack Rodwell available again after a groin strain kept him out of the clash with Liverpool, however Everton will be without the ineligible Lucas Neill and John Heitinga, while Leon Osman (foot) is an injury casualty.
Tony Hibbert is set to equal Everton’s European appearance record – 19 matches – which is jointly held by Colin Harvey and Brian Labone.
Kick-off at the Olympic Stadium in Athens is at 6pm GMT.
Everton (from): Howard, Hibbert, Baines, Distin, Coleman, Mustafi, Gosling, Duffy, Cahill, Rodwell, Pienaar, Bilyaletdinov, Fellaini, Jo, Saha, Baxter, Yakubu, Akpan, Nash.